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Biomedical subjects

D G Pfister

Publications and source records attributed to D G Pfister.

12 recordsLinked to original sources

Base-of-tongue cancer treated with external beam irradiation plus brachytherapy: oncologic and functional outcome.

Between January 1981 and June 1990, 36 previously untreated patients with squamous cancer of the base of the tongue were treated with radiation therapy. This therapy consisted of a 5,000-5,400-cGy external beam plus a 2,000-3,000-cGy boost to the base of the tongue with an iridium-192 implant. Necks with negative nodes were only irradiated, while necks with positive nodes were treated with irradiation plus neck dissection. Actuarial local control and survival at 2 years were 87.5%. Neck control was achieved in 35 of 36 patients. When implantation was performed with the nonlooping technique, the injury rate was statistically higher than in patients who underwent implantation with the looping technique (P = .02). Thirty patients participated in a function assessment involving a Performance Status Scale for patients with head and neck cancer. The authors concluded that management of base-of-tongue cancer with external beam irradiation plus brachytherapy is both oncologically and functionally successful.

Adult

Current status of larynx preservation with multimodality therapy.

Patients with advanced squamous cell carcinoma of the head and neck often require total laryngectomy, but many patients will refuse the procedure despite the prospect of a lower cure rate. Radiation therapy alone can cure selected patients. Chemotherapy has been combined with radiation in a variety of ways, in hopes of improving local control, preserving function, and achieving survival better than that achieved with radiation therapy alone. Several studies have yielded encouraging results, including the only randomized study that has compared chemotherapy/radiation to standard total laryngectomy and postoperative radiation therapy. All function preservation treatment programs require a motivated and compliant patient, careful patient monitoring, and close cooperation among surgical, radiation, and medical oncologists.

Carcinoma, Squamous Cell

Genetic analysis as an aid in diagnosis for patients with midline carcinomas of uncertain histologies.

The tumors of nine patients with carcinomas of uncertain histogenesis (eight with poorly differentiated carcinomas involving primarily midline structures and one with a diagnosis of seminoma and atypical clinical features) were studied by cytogenetic and Southern blot analyses. Four of the eight patients with poorly differentiated carcinomas had abnormalities of chromosome 12 consistent with a diagnosis of germ cell tumor. These abnormalities comprised an i(12p) in two patients and a del(12q) in a third patient detected by cytogenetic analysis and multiple copies of 12p detected by Southern blot analysis in a fourth patient. Three of these four patients with a diagnosis of germ cell tumor established by genetic analysis achieved a complete response to cisplatin-based chemotherapy. The tumor biopsy of one patient showed a t(11;22) (q24;q12), and this patient had chemotherapy directed to neuroepithelioma. Cytogenetic analysis was unsuccessful for the tumors of three patients; these tumors did not have multiple copies of 12p detected by Southern blot analysis. These patients did not respond to cisplatin-based chemotherapy. One patient with a diagnosis of extragonadal seminoma failed to respond to cisplatin-based chemotherapy and had a second tumor biopsy performed that demonstrated a t(8;14) (q24;q32). This patient's diagnosis was changed to a non-Hodgkin's lymphoma. Thus, genetic analysis provided a diagnosis in six of nine patients. Cytogenetic and molecular analyses are useful clinical tools for the determination of histogenesis in some patients with poorly differentiated carcinomas of uncertain histology.

Adult

Concomitant chemotherapy-radiation therapy followed by hyperfractionated radiation therapy for advanced unresectable head and neck cancer.

In January 1988, we initiated a prospective study evaluating a new treatment approach with chemotherapy and radiotherapy for unresectable head and neck cancer. Weeks 1-4 were the initial debulking phase. Radiotherapy was delivered using 1.8 Gy/day to large portals including gross disease and all areas at risk. Cisplatinum, 100mg/m2, was given concomitant with radiotherapy on days 1 and 22. Weeks 5 and 6 were the boosting phase. This involved twice-a-day irradiation. The AM fraction of 1.8 Gy was given to the entire area at risk, whereas the PM dose of 1.6 Gy was limited to the gross disease alone. Thus a total of 70 Gy/6 weeks was delivered. A total of 24 patients were treated, 22 of whom have completed this protocol and are evaluable. All patients had massive disease, with 15 having gross involvement of brain, orbit, skull base, or carotid artery. Follow-up ranged from 3-22 months (median 12 months). Major responses were achieved in 96%, with 64% complete responses and 32% partial responses. Two patients with PR were able to undergo complete surgical resection, making the overall rate of complete response, including surgery, 73%. At 1 year, actuarial survival was 69%, and local progression-free survival was 56%. Distant metastases developed in 5 (23%). This approach appears both safe and effective in producing excellent regression and local control for far advanced head and neck cancer. More time is needed to see if these results are sustained. Efforts to build upon this experience appear warranted.

Adenocarcinoma

Larynx preservation with combined chemotherapy and radiation therapy in advanced but resectable head and neck cancer.

Forty patients with advanced, resectable squamous cell carcinoma of the larynx, oropharynx, or hypopharynx whose surgery would have required total laryngectomy (TL), were treated with one to three cycles of cisplatin-based chemotherapy before local therapy with the goal of larynx preservation. Clinical complete responses (CRs) or partial responses (PRs) to chemotherapy were seen in 26 of 40 patients (65%). Three patients with primary-site disease unresponsive to chemotherapy underwent resection of the primary lesion and neck dissection followed by radiation therapy (RT). Thirty-seven patients were referred after chemotherapy for RT +/- neck dissection. Thirty-one of 40 patient (78%) were rendered disease-free (no evidence of disease [NED]). With a median follow-up of 49 months (range, 31 to 76), the overall actuarial survival rate for the group was 58% at 2 years and 33% at 5 years. The failure-free survival rate was 42% and 33% at 2 and 5 years, respectively. Seven patients refused recommended TL throughout their course. This may have adversely affected survival results. A greater proportion of patients who achieved a CR or PR to chemotherapy remained disease-free compared with those who achieved less than a PR (P less than .001). Sixteen patients relapsed, 10 with locoregional disease. Six patients underwent TL, either for initial induction failure or at relapse, for an actual larynx-preservation rate of 34 of 40 patients (85%). If the seven patients who refused TL are included, the anticipated preservation rate is 27 of 40 patients (68%). Larynx preservation with combined chemotherapy and radiation is feasible and effective in patients with advanced, resectable squamous cell carcinoma of the head and neck (SCHN). This treatment approach requires a motivated patient, careful patient monitoring, and close interdisciplinary cooperation among oncologists.

Adult

Chemotherapy as part of the initial treatment for nasopharyngeal cancer.

Although external beam radiation therapy is the standard treatment for nasopharyngeal carcinoma, there has been increasing interest in the use of adjunctive chemotherapy. Unfortunately, studies evaluating its role in this disease are retrospective, and have included significant numbers of patients who would have done well with external beam radiation therapy alone. The authors have reviewed the available literature on adjunctive chemotherapy for cancer of the nasopharynx and have attempted to define which patients should be considered for study. They have concluded that no patients should be treated with systemic therapy outside of an investigational protocol, and that these protocols should only include those with T3, T4, N2 or N3 disease. Programs using optimal cisplatin-containing regimens and those using concomitant chemotherapy and external beam radiation therapy warrant further attention.

Antineoplastic Agents

Classifying clinical severity to help solve problems of stage migration in nonconcurrent comparisons of lung cancer therapy.

To compare the effects of stage migration in the "traditional" 3-stage TNM (tumor, node, metastasis) system with those in a new "expanded" 5-stage system, which has two additional stages for the poor prognostic groups, we used both systems to classify a cohort of 178 patients with primary lung cancer. To check for migrations, the stages in both systems were first assigned using only "old" technological information and were then reassigned using all the available "new" as well as old technological data. Although the 5-stage system had more migrations than the 3-stage system, survival rates were relatively unaffected for patients in the two new stages with poor prognosis. In both TNM staging patterns, the effects of stage migration on survival statistics were most impressive in the prognostically better (TNM I and II) stages. A solution to the migration problem is offered by the "clinical severity" (CS) staging system. Like the expanded TNM system, the CS system has 5 stages and a sharp prognostic gradient among stages. The CS system, however, had fewer technology-induced stage migrations than either TNM system, and the migrations had no substantial impact on stage-specific survival results. The excellent prognostic discrimination and secular stability of the CS system make it superior to the TNM system for comparing treatment results from different eras, especially for patients with stage I and II disease.

Humans

Carboplatin, etoposide, and bleomycin for patients with poor-risk germ cell tumors.

A prospective study of four cycles of carboplatin (CBDCA) + etoposide + bleomycin (EBC) was conducted in 32 previously poor-risk nonseminomatous germ cell tumor (GCT) patients and the results compared with past studies. Patients with extragonadal (nine patients) and testicular nonseminomatous GCT with a probability of complete response (CR) less than 0.5 as calculated by a mathematical model using marker values and number of metastatic sites (23 patients) were included. Nineteen patients (59%) achieved a CR and 14 complete responders (43%) remain free of disease. The overall and durable CR proportions were similar to those observed in prior poor-risk studies at Memorial Sloan-Kettering Cancer Center. Myelosuppression was the major toxicity. Based on the low CR proportion, EBC is no better than other standard programs for poor-risk GCT. However, its ease of administration as an outpatient, mild renal and gastrointestinal toxicity, and efficacy comparable to cisplatin-based chemotherapy used in prior poor-risk trials at Memorial Sloan-Kettering Cancer Center warrant a Phase III trial comparing CBDCA-based and cisplatin-based chemotherapy for good-risk GCT patients.

Adolescent

Diagnostic criteria and technology as sources for changing incidences of pulmonary diseases.

PURPOSE: To investigate the impact of changes in diagnostic criteria and technology on the rates of occurrence of pulmonary diseases during each of four different calendar years: 1921, 1941, 1961, and 1982. PATIENTS AND METHODS: The medical records were obtained for all patients discharged from Yale-New Haven Hospital during 1921, 1941, 1961, and 1982 with a diagnosis of either pulmonary tuberculosis or primary lung cancer. Each patient's entire clinical course was then thoroughly reviewed, including all available data obtained in the six-month intervals before and after the patient's hospitalization. Critical diagnostic information obtained during life at any time during this one-year period was acceptable as evidence for the diagnosis. RESULTS: According to modern diagnostic criteria, the existing evidence of pulmonary tuberculosis or primary lung cancer often did not justify those diagnoses in patients hospitalized during each of the four survey years. The proportions of justified diagnoses showed a consistent increase over time: 16%, 42%, 53%, and 86%, respectively, for tuberculosis, and 0%, 54%, 93%, and 93%, respectively, for lung cancer. CONCLUSION: The results suggest that some of the statistical changes in occurrence rates for these two pulmonary diseases may be due to temporal improvements in diagnostic precision, not just to environmental changes or therapeutic advances.

Diagnosis, Differential

The rightward shift of colon cancer. Aging or artifact?

The results of a cross-sectional study were recently used as the primary basis for postulating a causal relationship between aging and the observed increasing proportion of right-sided colorectal carcinoma diagnosed in recent decades. However, cross-sectional research methodologies are more prone than cohort designs to biases that may produce misleading results, especially those biases due to differences in disease detection and in patient losses among study groups. A hypothetical prospective cohort model is used to help illustrate these methodological limitations. Other data reviewed appear not to support the "aging gut" hypothesis. Additional information using more robust methodologies will be needed to delineate the role of aging in the shift in location of colorectal carcinoma.

Aged